Preparation of Nanoemulsions by Premix Membrane Emulsification: Which Parameters Have a Significant Influence on the Resulting Particle Size?

Oil-in-water emulsions with particle sizes smaller than 200 nm are interesting carrier systems for poorly water-soluble drugs. Such emulsions can be produced by premix membrane emulsification. In this study, it was systematically investigated which process and formulation parameters have a strong influence on the resulting quality of a triglyceride emulsion. The influence of the pre-emulsion quality and the emulsifier concentration was examined. Also a design of experiments (DoE) approach was carried out: variables included were emulsifier (poloxamer 188, Tween 80, and sucrose laurate [SL]), flow rate, cycle number, and membrane material (polyester, nylon, cellulose acetate, and aluminum oxide; pore sizes, 200 nm), and responses were d50 value and span for particle size and distribution width. The quality of the pre-emulsion had no influence on the quality of the nanoemulsion after 5 extrusion cycles. The DoE evaluation indicated that an increase in flow rate was of minor importance, whereas an increase in cycle number had a strong impact on the decrease of particle size. The very hydrophilic alumina membrane in combination with the emulsifier which caused the lowest interfacial tension (SL) was the most suitable combination. However, in general, the favorable emulsifier was membrane dependent. Even smaller particle sizes (∼100 nm) could be achieved by using an alumina membrane with smaller pore sizes (100 nm).